Use of Clinical Trial Characteristics to Estimate Costs of New Drug Development.

Importance: Despite their importance to patients, health, and industry, the magnitude of investments in drug research and development (R&D) remain nebulous. New policies require more granular and transparent R&D cost estimates to better balance incentives for innovation and returns to developers.

Objective: To estimate per-drug R&D costs using a novel, reproduceable approach and to describe firm-level R&D costs per discrete unit of R&D activity (1 patient-month).

Glucarpidase for Treatment of High-Dose Methotrexate Toxicity.

High-dose methotrexate (MTX) results in high rates of acute kidney injury (AKI), neutropenia, and hepatotoxicity. Glucarpidase is a recombinant enzyme that cleaves MTX, but clinical data supporting its use are scarce. We examined the association between glucarpidase administration and outcomes in adults with MTX-AKI from 28 cancer centers across the U.

The Effects of alfapump on Ascites Control and Quality of Life in Patients with Cirrhosis and Recurrent or Refractory Ascites.

Aim: To assess the safety and efficacy of alfapump on ascites control and quality of life in these patients.

Methods: Patients with cirrhosis and RA requiring ≥2 TPs 30 days prior were enrolled and followed for 24 months (M) post-implant. Primary efficacy endpoint assessed at 6M was reduction in paracentesis requirement; safety end point was device related adverse events resulting in intervention, explant, or death.

Care Fragmentation Following Bariatric Operations: A National Analysis.

Background: Although existing work has evaluated outcomes associated with care fragmentation (CF), these adverse consequences may be accentuated in patients undergoing bariatric operations. This retrospective study examined the association of CF with clinical and financial outcomes among patients receiving bariatric surgery.

Methods: All adult (≥18 years) records for bariatric operations were tabulated from the 2016-2021 Nationwide Readmissions Database.

Investigating Racial, Ethnic, and Socioeconomic Disparities in Pelvic Organ Prolapse Surgery.

Importance: Racial/ethnic and socioeconomic disparities have been observed in the mode of pelvic organ prolapse surgery. Some of the disparities may be attributed to differences in access to care and advanced surgical technology across the United States, although this is difficult to study.

Objective: We aimed to investigate whether racial/ethnic or socioeconomic disparities in a mode of prolapse surgery exist in a managed care setting, where differences in access are minimized.

Civic identity: media, belonging, & Latiné youth in the 2020 US presidential election.

We explore how Latiné immigrant-origin youth used and made sense of media to enact their civic identities during the 2020 US presidential election cycle. In a polarized national context, this project highlights the voices and experiences of the participants (n=39). We conducted and analysed semi-structured interviews to identify three comprehensive themes.

Warm Autoimmune Hemolytic Anemia as a Rare Presentation of Pre-fibrotic Primary Myelofibrosis.

Primary myelofibrosis (PMF) is an uncommon chronic myeloproliferative disorder that is commonly associated with Janus kinase 2 (JAK-2), calreticulin (CALR), or thrombopoietin receptor (MPL) mutations. Pre-fibrotic PMF (also known as pre-PMF or early PMF) is a subtype of PMF that is defined by a lower grade of fibrosis. In this report, we present a rare case of warm autoimmune hemolytic anemia (wAIHA) associated with pre-PMF.

What Are the Trends in Women's Representation Among Principal Investigators of US Clinical Trials in the Field of Genetics?

Introduction: Despite progress in the representation of women in the medical profession, substantial gender disparities persist in leadership roles, particularly in clinical trials. Clinical trials are crucial to evidence-based medicine, offering visibility, career advancement, and future funding opportunities for principal investigators (PIs). However, women remain underrepresented in these roles, especially in genetics.

United States Pooled Cohort Cardiovascular Disease Risk Scores in Adults With Diabetes Mellitus.

Background: There is significant heterogeneity in cardiovascular disease (CVD) risk among patients with diabetes mellitus (DM).

Objectives: The purpose of this study was to develop risk scores for total CVD and its components from a contemporary pooled, observational cohort of U.S.

The Relationship Between Quantitative Ischemia, Early Revascularization, and Major Adverse Cardiovascular Events: A Multicenter Study.

Background: Observational data have suggested that patients with moderate to severe ischemia benefit from revascularization. However, this was not confirmed in a large, randomized trial.

Objectives: Using a contemporary, multicenter registry, the authors evaluated differences in the association between quantitative ischemia, revascularization, and outcomes across important subgroups.

Propensity Score Analysis of Possible Medication Effects on Outcomes in Patients With Systemic Right Ventricles.

Background: Patients with systemic right ventricle (SRV), either d-transposition of the great arteries following an atrial switch procedure or congenitally corrected transposition of the great arteries, develop severe right ventricular dysfunction, prompting appropriate medical therapy. However, the efficacy of beta-blockers and angiotensin receptor blockers or angiotensin-converting enzyme inhibitors (ACEI) in SRV patients is unproven.

Objectives: The objective of this study was to determine the effects of ACEI/ARB and beta-blockers on outcomes in SRV patients after accounting for likely cofounders affecting their use.

The Multifaceted Roles of Neutrophil Death in COPD and Lung Cancer.

Chronic obstructive pulmonary disease (COPD) and lung cancer are closely linked, with individuals suffering from COPD at a significantly higher risk of developing lung cancer. The mechanisms driving this increased risk are multifaceted, involving genomic instability, immune dysregulation, and alterations in the lung environment. Neutrophils, the most abundant myeloid cells in human blood, have emerged as critical regulators of inflammation in both COPD and lung cancer.

Addressing the unmet need in NSCLC progression with advances in second-line therapeutics.

Lung cancer is the leading cause of cancer mortality globally, with non-small cell lung cancer (NSCLC) accounting for 85% of cases. Despite advancements in first-line treatments such as immunotherapy and targeted therapies, resistance to these treatments is common, creating a significant unmet need for effective second-line therapies. This review evaluates current and emerging second-line therapeutic options for advanced or metastatic NSCLC, focusing on their efficacy and potential to improve patient outcomes.

The GD-1 Stellar Stream Perturber as a Core-collapsed Self-interacting Dark Matter Halo.

The GD-1 stellar stream exhibits spur and gap structures that may result from a close encounter with a dense substructure. When interpreted as a dark matter subhalo, the perturber is denser than predicted in the standard cold dark matter (CDM) model. In self-interacting dark matter (SIDM), however, a halo could evolve into a phase of gravothermal collapse, resulting in a higher central density than its CDM counterpart.

Case report: High-grade serous tubo-ovarian carcinoma with fusion and insights into targetability.

fusion is one of the classes of emerging therapeutic targets of precision oncology and is observed in many solid tumor types. Our understanding of oncogenic mechanisms and therapy effects of molecular targets tends to reflect those occurring in overrepresented tumor types, posing a challenge in therapy planning of the same targets occurring in unusual tumor types. We present a case of a primary high-grade serous tubo-ovarian carcinoma with a novel fusion, an exceedingly rare combination of tumor type and fusion class, with an unusually short-lived response to futibatinib.

Increased gastrointestinal bleeding-related mortality during the COVID-19 pandemic.

Background: Despite its significant health burden, there is a lack of national-level temporal patterns in gastrointestinal bleeding (GIB) mortality.

Objectives: To comprehensively decipher the annual and monthly trend of GIB-related mortality in the United States.

Design: Cross-sectional study.

Trends and Outcomes in Sarcomatoid Renal Cell Carcinoma: Analysis of the National Cancer Data Base.

Background And Objective: Our aim was to determine the clinical characteristics, temporal trends, and survival outcomes for sarcomatoid-dedifferentiated renal cell carcinoma (sRCC), as sRCC has historically had poor prognosis and a contemporary cohort has not been well characterized in a population-based study.

Methods: Data for 302 630 RCC cases from 2010 to 2019 were extracted from the National Cancer Data Base, of which 4.1% (12 329) were sRCC.

Nicotine and cannabis vaping among early high school adolescents: Disparities of use across sociodemographic characteristics and associations with psychosocial factors.

This study examines whether adolescent nicotine and cannabis vaping types (i.e., nicotine-only, cannabis-only, and dual use) differ across sociodemographic and school characteristics (e.

Changing Treatment and Metastatic Disease Patterns in Patients with EGFR Mutated NSCLC: An Academic Thoracic Medical Investigator's Consortium Registry Analysis.

Introduction: Osimertinib is now a standard first-line (1L) therapy for EGFR-mutated (EGFRm) advanced NSCLC. We aimed to characterize patterns of therapy and longitudinal risk of brain and liver metastasis in a cohort of EGFRm NSCLC.

Methods: Patients with metastatic EGFRm NSCLC who received 1L systemic therapy at sites within the Academic Thoracic Medical Investigator's Consortium were included; demographic and clinical data including treatment patterns were described.

Feasibility and psychometric quality of smartphone administered cognitive ecological momentary assessments in women with metastatic breast cancer.

Objective: Metastatic breast cancer (MBC) is associated with burdensome side effects, including cognitive changes that require ongoing monitoring. Cognitive ecological momentary assessments (EMAs) allow for assessment of individual cognitive functioning in natural environments and can be administered via smartphones. Accordingly, we sought to establish the feasibility, reliability, and validity of a commercially available cognitive EMA platform.

Deep Learning to Predict the Future Growth of Geographic Atrophy from Fundus Autofluorescence.

Purpose: The region of growth (ROG) of geographic atrophy (GA) throughout the macular area has an impact on visual outcomes. Here, we developed multiple deep learning models to predict the 1-year ROG of GA lesions using fundus autofluorescence (FAF) images.

Design: In this retrospective analysis, 3 types of models were developed using FAF images collected 6 months after baseline to predict the GA lesion area (segmented lesion mask) at 1.

Predicting Antidepressant Treatment Response From Cortical Structure on MRI: A Mega-Analysis From the ENIGMA-MDD Working Group.

Accurately predicting individual antidepressant treatment response could expedite the lengthy trial-and-error process of finding an effective treatment for major depressive disorder (MDD). We tested and compared machine learning-based methods that predict individual-level pharmacotherapeutic treatment response using cortical morphometry from multisite longitudinal cohorts. We conducted an international analysis of pooled data from six sites of the ENIGMA-MDD consortium (n = 262 MDD patients; age = 36.

Long-term Complications From Peripheral Nerve Blocks After Pediatric Orthopaedic Lower Extremity Procedures: A Systematic Review.

Background: Peripheral nerve blocks (PNBs) are frequently utilized as a regional anesthetic in pediatric orthopaedic surgery for postoperative pain control and reduced time to discharge; however, short- and long-term complications after these procedures are variably reported.

Purpose: To identify the frequency of long-term complications in pediatric patients who received regional anesthesia for a lower extremity orthopaedic procedure.

Study Design: Systematic review; Level of evidence, 4.

Two-year follow-up of dementia caregivers after a digital health intervention WECARE: a mixed-method study.

Objectives: Few digital health interventions for dementia caregivers, especially for racial and ethnic minorities, include long-term follow-ups. This study assessed the feasibility of two-year follow-up of the Wellness Enhancement for Caregivers (WECARE) intervention for Chinese American dementia caregivers, examined the changes in psychosocial health and explored future strategies.

Method: A mixed-method study was conducted two years after the initial WECARE intervention trial.